Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program

Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program

Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection giv...

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Veröffentlicht in:European heart journal 2020-11, Vol.41 (Supplement_2)
Hauptverfasser: Van Tassell, B, Wohlford, G.F, Ho, A.C, Vecchie, A, Garmendia, C, Trankle, C.R, Buckley, L.F, Kadariya, D, Canada, J.M, Carbone, S, Markley, R, Turlington, J.S, Appleton, D, Lipinski, M.J, Abbate, A
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container_issue Supplement_2
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container_title European heart journal
container_volume 41
creator Van Tassell, B
Wohlford, G.F
Ho, A.C
Vecchie, A
Garmendia, C
Trankle, C.R
Buckley, L.F
Kadariya, D
Canada, J.M
Carbone, S
Markley, R
Turlington, J.S
Appleton, D
Lipinski, M.J
Abbate, A
description Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P
doi_str_mv 10.1093/ehjci/ehaa946.1728
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We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P&lt;0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1093/ehjci/ehaa946.1728</identifier><language>eng</language><publisher>Oxford University Press</publisher><ispartof>European heart journal, 2020-11, Vol.41 (Supplement_2)</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Van Tassell, B</creatorcontrib><creatorcontrib>Wohlford, G.F</creatorcontrib><creatorcontrib>Ho, A.C</creatorcontrib><creatorcontrib>Vecchie, A</creatorcontrib><creatorcontrib>Garmendia, C</creatorcontrib><creatorcontrib>Trankle, C.R</creatorcontrib><creatorcontrib>Buckley, L.F</creatorcontrib><creatorcontrib>Kadariya, D</creatorcontrib><creatorcontrib>Canada, J.M</creatorcontrib><creatorcontrib>Carbone, S</creatorcontrib><creatorcontrib>Markley, R</creatorcontrib><creatorcontrib>Turlington, J.S</creatorcontrib><creatorcontrib>Appleton, D</creatorcontrib><creatorcontrib>Lipinski, M.J</creatorcontrib><creatorcontrib>Abbate, A</creatorcontrib><title>Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program</title><title>European heart journal</title><description>Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P&lt;0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)</description><issn>0195-668X</issn><issn>1522-9645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqNUctq4zAUFUMHJn38QFf6AbeSHcvS7ELoCwqFNh1mZ67lq0QZ2zKSXMjnzZ9VTvoB3dzL4bwWh5Brzm44U8Ut7vbapgugluKGV7n8QRa8zPNMiWV5RhaMqzITQv79Rc5D2DPGpOBiQf6_onZ9YwcYIn0aIvoOp392yDj1qHGMztNEwdYNNkRqEow7pNEjxB6Txxn6tskCbo8IO_yAaN1AQU8RaX9wGnxroaN2MOD1kRs9fiR1oGaKk0e6Q_ApG2w3oxP3mwIdneuwTf3QHYINc9dc_mf9vnrdpBS39dBfkp8GuoBXX_-CbO7vNuvH7Pnl4Wm9es605DLTpqpapQoQy7aRhVbQVizXHBUYlEroSrRSGmWMaJC3TZHnJZY5g0YpaQpZXJD8FKu9C8GjqUdve_CHmrN63qA-blB_bVDPGyRTdjK5afyO_hN_q5JE</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Van Tassell, B</creator><creator>Wohlford, G.F</creator><creator>Ho, A.C</creator><creator>Vecchie, A</creator><creator>Garmendia, C</creator><creator>Trankle, C.R</creator><creator>Buckley, L.F</creator><creator>Kadariya, D</creator><creator>Canada, J.M</creator><creator>Carbone, S</creator><creator>Markley, R</creator><creator>Turlington, J.S</creator><creator>Appleton, D</creator><creator>Lipinski, M.J</creator><creator>Abbate, A</creator><general>Oxford University Press</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20201101</creationdate><title>Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program</title><author>Van Tassell, B ; Wohlford, G.F ; Ho, A.C ; Vecchie, A ; Garmendia, C ; Trankle, C.R ; Buckley, L.F ; Kadariya, D ; Canada, J.M ; Carbone, S ; Markley, R ; Turlington, J.S ; Appleton, D ; Lipinski, M.J ; Abbate, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c818-cf77d993a64db83c9ad702c1e9afe896c76d88f9ff6be1db3225e520ab998f383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Tassell, B</creatorcontrib><creatorcontrib>Wohlford, G.F</creatorcontrib><creatorcontrib>Ho, A.C</creatorcontrib><creatorcontrib>Vecchie, A</creatorcontrib><creatorcontrib>Garmendia, C</creatorcontrib><creatorcontrib>Trankle, C.R</creatorcontrib><creatorcontrib>Buckley, L.F</creatorcontrib><creatorcontrib>Kadariya, D</creatorcontrib><creatorcontrib>Canada, J.M</creatorcontrib><creatorcontrib>Carbone, S</creatorcontrib><creatorcontrib>Markley, R</creatorcontrib><creatorcontrib>Turlington, J.S</creatorcontrib><creatorcontrib>Appleton, D</creatorcontrib><creatorcontrib>Lipinski, M.J</creatorcontrib><creatorcontrib>Abbate, A</creatorcontrib><collection>CrossRef</collection><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Tassell, B</au><au>Wohlford, G.F</au><au>Ho, A.C</au><au>Vecchie, A</au><au>Garmendia, C</au><au>Trankle, C.R</au><au>Buckley, L.F</au><au>Kadariya, D</au><au>Canada, J.M</au><au>Carbone, S</au><au>Markley, R</au><au>Turlington, J.S</au><au>Appleton, D</au><au>Lipinski, M.J</au><au>Abbate, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program</atitle><jtitle>European heart journal</jtitle><date>2020-11-01</date><risdate>2020</risdate><volume>41</volume><issue>Supplement_2</issue><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Abstract Background ST segment elevation myocardial infarction (STEMI) is associated with an intense acute inflammatory response and an increased risk of death and heart failure (HF). We analyzed the effect of recombinant interleukin-1 receptor antagonist (anakinra) 100 mg subcutaneous injection given once or twice daily for 14 days on the occurrence of HF in a pooled analysis of 3 clinical trials. Methods Enrollment criteria and study procedures were the same across the three studies. High-sensitivity C-reactive protein (CRP) was measured at baseline, 72 hours, and 14 days to construct an area under the curve (AUC0–14). Clinical events up to 1 year were adjudicated by an independent committee blinded to treatment allocation. Data for anakinra once daily and anakinra twice daily were pooled into a single anakinra group. CRP data are presented as median and interquartile range to allow for deviation from Gaussian distribution and non-parametric tests were used to evaluate differences between groups. Kaplan-Meier survival analyses were conducted and the intervention groups were compared using a log-rank test. Results Between 2008 and 2017, 139 patients with STEMI were enrolled. 84 patients were randomized to anakinra and 55 patients were randomized to placebo. Anakinra significantly reduced the CRP AUC0–14 (76 [42–147] vs 222 [117–339] mg*day/L; P&lt;0.001), the composite of death or HF hospitalization (Chi2=7.167; P=0.007), and the composite of death or new onset HF (Chi2=9.43; P=0.002) compared with placebo. Treatment with anakinra had no effect on ischemic events (composite of death, myocardial infarction, and unstable angina; (Chi2=0.574; P=0.45) or the composite of death, myocardial infarction and cerebrovascular accident (Chi2=0.065; P=0.80). Patients receiving anakinra had increased injection site reactions (20.2% vs 3.6%; P=0.005) but no change in infections (14.3% vs 9.1%, P=0.435) versus placebo. Conclusions Treatment with anakinra for 14 days following STEMI blunts the inflammatory response and appears to reduce the occurrence of HF events at 1 year. These results support the hypothesis that early and targeted modification of the inflammatory response in STEMI may be a viable strategy to improve patient outcomes. Adjudicated events at 1 year Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart Lung and Blood Institute (USA), American Heart Association (USA)</abstract><pub>Oxford University Press</pub><doi>10.1093/ehjci/ehaa946.1728</doi></addata></record>
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title Recombinant Interleukin-1 receptor antagonist for the treatment of ST-segment elevation acute myocardial infarction prevents future heart failure events: a pooled analysis of the VCUART program
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